The Endocannabinoid System.

What is the Endocannabinoid System?

Before discussing the functions of the endocannabinoid system (ECS), it is important to understand its components. The ECS is comprised of cannabinoid receptors, endogenous ligands (binding molecules) for those receptors, and enzymes that synthesize and degrade the ligands.

The most well known cannabinoid receptors are CB1 and CB2. Studies in the early 1990s provided initial evidence of the existence and purpose of CB1 and CB2 receptors. Both types of cannabinoid receptors are found throughout the entire body, but are distributed differently. CB1 receptors are concentrated primarily in the brain, while CB2 receptors are mainly found in the immune system. However, CB1 receptors are also distributed in a variety of peripheral areas like adipose (fat) tissue, and CB2 receptors are expressed to some degree in the brain.

The primary endocannabinoids are anandamide and 2-arachidonoyl glycerol (2-AG). Anandamide was discovered in 1992 and determined to be the endogenous ligand for the CB1 receptor. Its chemical structure is very similar to tetrahydrocannabinol. 2-AG was discovered in 1995, and unlike anandamide has a high affinity for activating both CB1 and CB2 receptors.

Anandamide and 2-AG are synthesized from arachidonic acid, an Omega-6 fatty acid, although the specific pathways and synthesizing enzymes vary. Anandamide is degraded by fatty acid amide hydrolase (FAAH), and 2-AG by monoacylglyceride lipase. Both endocannabinoids are manufactured “on demand” [as needed], using precursor molecules from cell membranes.

The Primary Function of the Endocannabinoid System.

The overall role of the ECS is described best by Dr. Dustin Sulak, the Director of Integr8 Health in Maine. His firm has treated thousands of patients with medicinal cannabis, and Dr. Sulak is one of the most sought-after speakers for medicinal cannabis conferences.

As Dr. Sulak discussed in an endocannabinoid introductory article, the primary function of endocannabinoid activity is to maintain a stable internal environment despite changes in the external environment. This stability is known as homeostasis, which endocannabinoids promote at the most basic levels. These endocannabinoids regulate homeostasis through a wide variety of mechanisms, including facilitation of intercellular communication between different cell types.

“At the site of an injury, for example, cannabinoids can be found decreasing the release of activators and sensitizers from the injured tissue, stabilizing the nerve cell to prevent excessive firing, and calming nearby immune cells to prevent release of pro-inflammatory substances. Three different mechanisms of action on three different cell types for a single purpose: minimize the pain and damage caused by the injury,” said Dr. Sulak.

When cells communicate, neurotransmitters normally flow from presynaptic neurons to postsynaptic neurons. Endocannabinoids are unique, being able to travel in the opposite direction and deliver feedback to the presynaptic cell. This process is a fundamental mechanism by which endocannabinoids maintain homeostasis. For example, if a neuron is firing messages too quickly, then endocannabinoids (usually 2-AG) instruct it to slow down by traveling upstream and activating presynaptic CB1 receptors.

Posted on September 1, 2015 .

Ethan Nadelmann: Why we need to end the War on Drugs

Is the War on Drugs doing more harm than good? In a bold talk, drug policy reformist Ethan Nadelmann makes an impassioned plea to end the "backward, heartless, disastrous" movement to stamp out the drug trade. He gives two big reasons we should focus on intelligent regulation instead.

Posted on August 28, 2015 .

Everything We Think We Know About Drug Violence Is Wrong

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Rosalio Reta was at summer camp, like all the other American teenagers his age. He was a short Texan fifteen-year old with spiky hair, nicknamed “Bart” because he looks like a less yellow Bart Simpson, and loves to skateboard. He was also into the Power Rangers, alternative pop, and Nintendo 64, especially The Mask of Zelda and Donkey Kong.

At camp in this particular year, he was learning useful skills, ones he will remember for the rest of his life. Only at this camp, you don’t learn how to canoe, or sing in a chorus, or make a log fire. You learn how to kill.

When I met him, he was 23, but he could still describe the techniques he learned here and later. Take beheading, for example. “There’s times I’ve seen it they’ve done it with a saw,” he told me through the prison glass. “Blood everywhere. When they start going they hit the jugular and –” he clicks his fingers – “[it’s] everywhere… They put the head right there. The head still moves, makes faces and everything. I think the nerves, you can see inside, the bone, everything’s moving. It’s like they’ve got worms. I’ve seen it move, when it’s on the ground. If he’s making a screaming face, it stays like that sometimes. Sometimes it slacks off.”

I have been thinking a lot about Rosalio as I read the media’s coverage of “drug-related violence.”

At the moment, it is widely believed in the US that what the media calls “drug-related violence” has a simple cause: a person uses drugs, goes crazy, and attacks somebody. That is what your media is telling you is happening all over the country.

I used to believe that too. But then I went on a 30,000-mile journey across a dozen countries to investigate the war on drugs for my book ‘Chasing The Scream: The First and Last Days of the War on Drugs’. I spent a lot of time with Chino Hardin, a transgendered former crack dealer in Brownsville, Brooklyn, and I met Rosalio through thick reinforced glass. (You can listen to my interviews with them here. I spoke to the leading academic experts on this, and pored over their research. And it turns out almost everything we have been told about drug-related violence is wrong.

Professor Paul Goldstein decided to look at every killing described as a “drug-related murder” in New York City in 1986, and he found something striking. It turned out 7.5 percent occurred after somebody took drugs and acted irrationally – the story the media presents as the whole picture. A further 2 percent were the result of addicts trying to steal to feed their habit and it going wrong. And all the rest – the vast and overwhelming majority – had a very different cause: one that has nothing to do with drug use at all.

The best way to understand it – and I was taught this by Chino, as he tutored me in the world of crack-dealing – is to imagine you wanted, as soon as you finish reading this article, to steal some vodka. You go to your local liquor store. You put it under your jacket. And if they catch you, they call the cops, and the cops will take you away. So that liquor store doesn’t need to be violent, or intimidating – they are backed with the power and force of the law to protect their property rights.

Now imagine you wanted to steal, not vodka, but (say) cannabis, or cocaine. If the guy in your neighborhood who sells them catches you, obviously, he can’t call the cops – they’d arrest him. So he has to fight you. He has to protect his property rights with violence. Now, obviously, he doesn’t want to be having a fight like that every day – so he has to establish a reputation for being so violent that nobody will dare to fuck with you. The best way to do that is to be terrifying, and to establish your reputation with a few theatrical acts of aggression.

As a dealer, you establish your patch against other dealers by force and terror, and you maintain your patch by force and terror. You don’t just hurt other dealers – you hurt cops, and any civilians who get caught in the cross-fire. The Nobel Prize-winning economist Milton Friedman calculated this dynamic causes an extra 10,000 killings every year in the US.

These killings have nothing to do with drugs – they are entirely to do with prohibition. Al Capone wasn’t getting drunk and shooting people up; the St Valentine’s Day massacre in Chicago, at the height of alcohol prohibition, wasn’t carried out by alcoholics. He was killing people to protect his product in a prohibited market. When alcohol prohibition ended, all that violence ended. Ask yourself: where are the violent alcohol-dealers today? Does the head of Smirnoff go and shoot the head of Heinneken in the face? Of course not. It’s not the alcohol that has changed. It’s the decision to stop banning it, and so to take it back from armed criminal gangs, and give it to licensed and regulated legal sellers. If milk was banned, and people still wanted milk, exactly the same process would take place.

This is what is causing the majority of the drug-related violence in the US. The killings that are rocking Chicago – the city Al Capone dominated under the last great wave of prohibition – are just one example, and a huge number of people are being caught in the cross-fire. To pluck just one example: Hadiya Pendleton was a 15-year old cheerleader who performed at President Obama’s inauguration, and was shot by a dealer aiming at another dealer.

This is terrible enough in the US. It is even more horrific in Northern Mexico, where I went for the book, and where Rosalio butchered or beheaded around 70 people, between the ages of 13 and 17. He was sent to his summer camp by one of the deadliest cartels – the Zetas. These gangs control the massive drug trade that runs through the country to supply the US and Europe, and they have simply taken over great swathes of the country. As a result, more than 100,000 people have been killed – for exactly the same reasons the small-time dealer in Kalgoorie was cut up.While Donald Trump shrieks about the border being insecure, he fails to see that the single biggest cause of violence along the border is a policy imposed by the US on the rest of the world.

This violence can be ended, if we make a better choice.

How can I be so sure? I studied the evidence from the US: it only started once the trade was criminalized, and transferred to criminals. And – even more crucially – I went to the countries that have moved beyond the drug war. For example, I went to Switzerland, where heroin has been made legal for addicts, who get it from clinics. The most detailed academic study, by Professor Ambrose Uchtenhagen, found 55% fewer vehicle thefts and 80% fewer muggings and burglaries, and a fall in crime that was – as the study puts it – “almost immediate.”

Do you know how many violent heroin dealers there are now in Switzerland? None. They don’t exist.

There were no violent drug-dealers before the war on drugs; and there are no violent drug dealers after the war on drugs.

But some people worry, totally understandably – wouldn’t there be a big increase in drug use, and therefore the (much smaller, but real) violent crime rate among users? I too was worried about this. But I went to Portugal, where they decriminalized all drugs – and transferred all the money they used to spend on punishing users and addicts, into helping them to turn their lives around instead. Injecting drug use fell by 50 percent, and crimes caused by addicts are significantly down.

When you end the drug war, you can reduce the small amount of violence caused by drug users, and end the huge amount of violence caused by drug dealers.

I stared at Rosalio through thick reinforced glass in a prison in rural Texas. He will be released – if he makes it that long – when he is in this mid-80s, six decades from now. I keep wondering: by the time he feels the sun on his face, will the war he fought and killed for still be raging across the world – or will we have chosen a sane path, at last?

This article draws on material from Johann Hari’s New York Times best-seller ‘Chasing The Scream: The First and Last Days of the War on Drugs’; other articles published elsewhere have also drawn on this material. To find out why it is the only book to ever be praised by everyone from Bill maher to Elton John to Glenn Greenwald, go to www.chasingthescream.com or to www.facebook.com/chasingthescream

You can follow Johann on Twitter at www.twitter.com/johannhari101

 

Posted on August 28, 2015 .

Marijuana Book Review – The Kitchen

 ’The Kitchen’ is the story of two men and their mission to grow world class marijuana.

The Kitchen’ highlights their struggles and their successes. I like that the book takes a very personal approach to teaching people about growing marijuana. Most grow books I’ve read over the years read more like textbooks than they do grow books based off of personal experiences. Growing marijuana is not easy, and living the life of a marijuana grower is not easy either. This book captures both of those struggles better than any other book I’ve ever read. It’s one thing to read a book and see a bunch of scientific jargon, and then have to show it to your friends and family to make sense out of it. It’s far better to read about what others have tried, what has worked and what hasn’t, and incorporate that into ones garden.

The same struggles that the books authors went through, Jay J. Kitchen and Uncle Tweezy, are the same struggles that you will go through as marijuana grower, or likely have already gone through if you are an experienced grower. This book is part grow guide, part adventure tales, part how-to be a marijuana consumer, all with unparalleled pictures of marijuana. In addition to telling the tale of two marijuana growers, ’The Kitchen’ includes guides on how to make ice water hash, how to roll a blunt, and how to roll a joint.

If there’s one thing that people will notice very quickly when they pick up this book, it is the pictures. Someone clearly got an ‘A’ in photography class! The pictures are huge, of a very high quality, and include every type of picture of marijuana you would ever want to see. The book includes pictures of over twenty of the most popular marijuana strains on the planet. There are pictures of the strains growing and pictures of the strains dried, all of which will make your mouth water. If you like nug porn, this book is absolutely for you. Below is information about the book via a press release that was put out when the book was launched:

Visually stunning, over-sized, and lavishly photographed, “THE KITCHEN” is both a gorgeous guide to growing marijuana and a riveting story about the authors’ (Jay J. Kitchen and Uncle Tweezy) quest to grow the most beautiful cannabis flowers possible in a small urban space in a major North American city.

The authors describe both hydroponic and soil growing technique in detail; instructions on making ice water hashish; how to roll both a joint and a blunt for the uninitiated or curious. Sumptuous photography documents the natural beauty of twenty varieties of marijuana selected from the seed stock of the world’s most renowned seed breeders, including Serious Seeds, Uptowngrowlab, Greenhouse Seed Company and DNA/ Reserva Privada Seed Company, among others.

“This book has been a long fascinating journey for me- its publication is the culmination of a dream, a passion project realized. I’m very happy to share it with my fellow aficionados” says author Jay J. Kitchen.

I would highly recommend this book to anyone that is a true fan of marijuana. I don’t know that I’ve ever seen another book that so accurately captures the experience of being a marijuana grower, and the evolution of a marijuana garden as a grower improves their skill set over time. For those that are new to marijuana growing, this book is a must because not only does it give the reader a lot of insight on how to grow marijuana, it provides first hand experiences of what not to do, in addition to what to do, which is something that every marijuana grower needs to know as they embark on the same journey that the authors of ‘The Kitchen’  have traveled.

‘The Kitchen’ is a very unique marijuana book, is very well written, and has a high production value that is virtually unmatched in marijuana literature. It’s not the type of book that you just put on a shelf – this book needs to be out where people can see it and enjoy it. This book is not just a marijuana grow guide. It’s SO much more.  If you are looking to beef up your own marijuana book collection, or are looking for a great gift idea for the marijuana consumer in your life, you should pick up a copy today. You won’t be disappointed.

‘The Kitchen’ can be purchased on Amazon. Check out ‘The Kitchen’ on Facebook. For another review of this book, check out LadyBud.Com. Source.

Posted on August 25, 2015 and filed under Story.

Recent Research on Medical Marijuana

Emerging Clinical Applications For Cannabis & Cannabinoids
A Review of the Recent Scientific Literature, 2000 — 2013

Humans have cultivated and consumed the flowering tops of the female cannabis plant, colloquially known as marijuana, since virtually the beginning of recorded history. Cannabis-based textiles dating to 7,000 B.C.E have been recovered in northern China, and the plant’s use as a medicinal and mood altering agent date back nearly as far. In 2008, archeologists in Central Asia discovered over two-pounds of cannabis in the 2,700-year-old grave of an ancient shaman. After scientists conducted extensive testing on the material’s potency, they affirmed, “[T]he most probable conclusion … is that [ancient] culture[s] cultivated cannabis for pharmaceutical, psychoactive, and divinatory purposes.”

Modern cultures continue to indulge in the consumption of cannabis for these same purposes, despite a present-day, virtual worldwide ban on the plant’s cultivation and use. In the United States, federal prohibitions outlawing cannabis’ recreational, industrial, and therapeutic use were first imposed by Congress under the Marihuana Tax Act of 1937 and then later reaffirmed by federal lawmakers’ decision to classify marijuana — as well as all of the plant’s organic compounds (known as cannabinoids) — as a Schedule I substance under the Controlled Substances Act of 1970. This classification, which asserts by statute that cannabis is equally as dangerous to the public as is heroin, defines cannabis and its dozens of distinct cannabinoids as possessing ‘a high potential for abuse, … no currently accepted medical use, … [and] a lack of accepted safety for the use of the drug … under medical supervision.’ (By contrast, cocaine and methamphetamine — which remain illicit for recreational use but may be consumed under a doctor’s supervision — are classified as Schedule II drugs; examples of Schedule III and IV substances include anabolic steroids and Valium respectively, while codeine-containing analgesics are defined by a law as Schedule V drugs, the federal government’s most lenient classification.) In July 2011, the Obama Administration rebuffed an administrative inquiry seeking to reassess cannabis’ Schedule I status, and federal lawmakers continue to cite the drug’s dubious categorization as the primary rationale for the government’s ongoing criminalization of the plant and those who use it. A three-judge panel for the US Court of Appeals for the District of Columbia affirmed the Administration’s position in 2013, arguing that a judicial review of cannabis’ federally prohibited status was not warranted at this time.

Nevertheless, there exists little if any scientific basis to justify the federal government’s present prohibitive stance and there is ample scientific and empirical evidence to rebut it. Despite the US government’s nearly century-long prohibition of the plant, cannabis is nonetheless one of the most investigated therapeutically active substances in history. To date, there are over 20,000 published studies or reviews in the scientific literature referencing the cannabis plant and its cannabinoids, nearly half of which were published within the last five years according to a key word search on the search engine PubMed Central, the US government repository for peer-reviewed scientific research. While much of the renewed interest in cannabinoid therapeutics is a result of the discovery of the endocannabinoid regulatory system (which is described in detail later in this booklet), some of this increased attention is also due to the growing body of testimonials from medical cannabis patients and their physicians.

The scientific conclusions of the overwhelmingly majority of modern research directly conflicts with the federal government’s stance that cannabis is a highly dangerous substance worthy of absolute criminalization.

For example, in February 2010 investigators at the University of California Center for Medicinal Cannabis Research publicly announced the findings of a series of randomized, placebo-controlled clinical trials on the medical utility of inhaled cannabis. The studies, which utilized the so-called ‘gold standard’ FDA clinical trial design, concluded that marijuana ought to be a “first line treatment” for patients with neuropathy and other serious illnesses.

Several of studies conducted by the Center assessed smoked marijuana’s ability to alleviate neuropathic pain, a notoriously difficult to treat type of nerve pain associated with cancer, diabetes, HIV/AIDS, spinal cord injury and many other debilitating conditions. Each of the trials found that cannabis consistently reduced patients’ pain levels to a degree that was as good or better than currently available medications.

Another study conducted by the Center’s investigators assessed the use of marijuana as a treatment for patients suffering from multiple sclerosis. That study determined that “smoked cannabis was superior to placebo in reducing spasticity and pain in patients with MS, and provided some benefit beyond currently prescribed treatments.”

A summary of the Center’s clinical trials, published in 2012 in the Open Neurology Journal, concluded: “Evidence is accumulating that cannabinoids may be useful medicine for certain indications. … The classification of marijuana as a Schedule I drug as well as the continuing controversy as to whether or not cannabis is of medical value are obstacles to medical progress in this area. Based on evidence currently available the Schedule I classification is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking.”

Around the globe, similarly controlled trials are also taking place. A 2010 review by researchers in Germany reports that since 2005 there have been 37 controlled studies assessing the safety and efficacy of marijuana and its naturally occurring compounds in a total of 2,563 subjects. By contrast, many FDA-approved drugs go through far fewer trials involving far fewer subjects.

As clinical research into the therapeutic value of cannabinoids has proliferated so too has investigators’ understanding of cannabis’ remarkable capability to combat disease. Whereas researchers in the 1970s, 80s, and 90s primarily assessed cannabis’ ability to temporarily alleviate various disease symptoms — such as the nausea associated with cancer chemotherapy — scientists today are exploring the potential role of cannabinoids to modify disease.

Of particular interest, scientists are investigating cannabinoids’ capacity to moderate autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease, as well as their role in the treatment of neurological disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis (a.k.a. Lou Gehrig’s disease.) In 2009, the American Medical Association (AMA) resolved for the first time in the organization’s history “that marijuana’s status as a federal Schedule I controlled substance be reviewed with the goal of facilitating the conduct of clinical research and development of cannabinoid-based medicines.”

Investigators are also studying the anti-cancer activities of cannabis, as a growing body of preclinical and clinical data concludes that cannabinoids can reduce the spread of specific cancer cells via apoptosis (programmed cell death) and by the inhibition of angiogenesis (the formation of new blood vessels). Arguably, these latter findings represent far broader and more significant applications for cannabinoid therapeutics than researchers could have imagined some thirty or even twenty years ago.

THE SAFETY PROFILE OF MEDICAL CANNABIS

Cannabinoids have a remarkable safety record, particularly when compared to other therapeutically active substances. Most significantly, the consumption of marijuana — regardless of quantity or potency — cannot induce a fatal overdose. According to a 1995 review prepared for the World Health Organization, “There are no recorded cases of overdose fatalities attributed to cannabis, and the estimated lethal dose for humans extrapolated from animal studies is so high that it cannot be achieved by … users.”

In 2008, investigators at McGill University Health Centre and McGill University in Montreal and the University of British Columbia in Vancouver reviewed 23 clinical investigations of medical cannabinoid drugs (typically oral THC or liquid cannabis extracts) and eight observational studies conducted between 1966 and 2007. Investigators “did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use” compared to non-using controls over these four decades.

That said, cannabis should not necessarily be viewed as a ‘harmless’ substance. Its active constituents may produce a variety of physiological and euphoric effects. As a result, there may be some populations that are susceptible to increased risks from the use of cannabis, such as adolescents, pregnant or nursing mothers, and patients who have a family history of mental illness. Patients with decreased lung function (such as chronic obstructive pulmonary disease) or those who have a history of heart disease or stroke may also be at a greater risk of experiencing adverse side effects from marijuana. As with any medication, patients should consult thoroughly with their physician before deciding whether the medical use of cannabis is safe and appropriate.

HOW TO USE THIS REPORT

As states continue to approve legislation enabling the physician-supervised use of medical marijuana, more patients with varying disease types are exploring the use of therapeutic cannabis. Many of these patients and their physicians are now discussing this issue for the first time and are seeking guidance on whether the therapeutic use of cannabis may or may not be advisable. This report seeks to provide this guidance by summarizing the most recently published scientific research (2000-2013) on the therapeutic use of cannabis and cannabinoids for 20 clinical indications.

In some of these cases, modern science is now affirming longtime anecdotal reports of medical cannabis users (e.g., the use of cannabis to alleviate GI disorders). In other cases, this research is highlighting entirely new potential clinical utilities for cannabinoids (e.g., the use of cannabinoids to modify the progression of diabetes.)

The conditions profiled in this report were chosen because patients frequently inquire about the therapeutic use of cannabis to treat these disorders. In addition, many of the indications included in this report may be moderated by cannabis therapy. In several cases, preclinical data and clinical data indicate that cannabinoids may halt the advancement of these diseases in a more efficacious manner than available pharmaceuticals.

For patients and their physicians, this report can serve as a primer for those who are considering using or recommending medical cannabis. For others, this report can serve as an introduction to the broad range of emerging clinical applications for cannabis and its various compounds.

Paul Armentano
Deputy Director
NORML | NORML Foundation
Washington, DC
January 7, 2014

* The author would like to acknowledge Drs. Dale Gieringer, Estelle Goldstein, Dustin Sulak, Gregory Carter, Steven Karch, and Mitch Earleywine, as well as Bernard Ellis, MPH, former NORML interns John Lucy, Christopher Rasmussen, and Rita Bowles, for providing research assistance for this report. The NORML Foundation would also like to acknowledge Dale Gieringer, Paul Kuhn, and Richard Wolfe for their financial contributions toward the publication of this report.

** Important and timely publications such as this are only made possible when concerned citizens become involved with NORML. For more information on joining NORML or making a donation, please visit: http://www.norml.org/join. Tax-deductible donations in support of NORML’s public education campaigns should be made payable to the NORML Foundation.

Foreword

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Introduction to the Endocannabinoid System

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Why I Recommend Medical Cannabis

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Alzheimer’s Disease

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Amyotrophic Lateral Sclerosis (ALS)

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Chronic Pain

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Diabetes Mellitus

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Dystonia

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Epilepsy

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Fibromyalgia

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Gastrointestinal Disorders

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Gliomas/Cancer

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Hepatitis C

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Human Immunodeficiency Virus (HIV)

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Huntington’s Disease

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Hypertension

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Incontinence

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Methicillin-resistant Staphyloccus aureus (MRSA)

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Multiple Sclerosis

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Osteoporosis

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Pruritus

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Rheumatoid Arthritis

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Sleep Apnea

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Tourette’s Syndrome

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Posted on August 24, 2015 and filed under Medical.